Receptor neurokinin

Neurokinin receptors NK2 receptor agonists (e.g. GR64349) have an anxiogenic profile in animal models while the antagonists (GR100679) have an anti-anxiety effect. However, NKi receptor antagonists have also been reported to have antianxiety activity in the social interaction test (File 1997). 

Anxiolytic agents, pyrido[l,2-a]benzimida-zoles as, 36 (1999) 169 Aromatase inhibition and breast cancer, 26 (1989) 253 33 (1996) 147 Arthritis neurokinin receptors in, 43 (2005) 53... 

A5 and C primarily project to lamina II and V of the dorsal horn, where they synapse onto local interneurons or directly onto upward-projecting neurons (figure 8.1). These primary afferents release a number of neurotransmitters to relay pain, including glutamate, aspartate, substance P, neurokinin A and B, and calcitonin gene-related peptide (table 8.1). NMDA, non-NMDA and neurokinin receptors are involved in re-... 

Tachykinins are among the most abundant neuropeptides in the central nervous system. Limbic structures, which are important in the control of emotional behaviors, in particular contain tachykinins and neurokinin receptor sites in high density (Honkaniemi et al. 1992 Hurd et al. 1999 Ribeiro-da-... 

Mizuta et al Expression and coupling of neurokinin receptor subtypes to inositol phosphate and calcium signaling pathways in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2008 294 L523. 

Ichinose, M., Nakajima, N., Takahashi, T., Yamauchi, H., Inoue, H., Takishima, T. Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist, Lancet 1992, 340, 1248-1251. 

Longmore, J., Hill, R. G., Hargreaves, R. J. Neurokinin-receptor antagonists pharmacological tools and therapeutic drugs, Can. J. Physiol. Pharmacol. 1997, 75, 612-621. 

Substance P is released from neurons and prefers to interact selectively with the neurokinin 1 (NK-1) subtype of neurokinin receptor (Figs. 5—68 to 5—70). Inter-... 

FIGURE 5—70. Substance P and neurokinin 1 receptors, part 3. Shown here is how substance P is formed from gamma PPT-A. Thus, substance P can be formed from three proteins derived from the PPT-A gene, namely, alpha, beta, and gamma PPT-A (see also Figs. 5-68 and 5-69). When substance P is released from neurons, it prefers to interact selectively with the neurokinin 1 subtype of neurokinin receptor (Figs. 5-68 to 5-70). However, there is a mismatch in the brain between the locations of substance P and the NK-1 receptors, suggesting that substance P acts preferentially by volume neurotransmission at sites remote from its axon terminals rather than by classical synaptic neurotransmission. 

Antagonists to all three neurokinin receptors (i.e., NK-1, NK-2, and NK-3) are now in clinical testing for a variety of indications, predominantly depression. Several are being tested in schizophrenia as well. 

Evidences for intermediate conformational states have also been observed in other receptors. Time-resolved peptide-binding studies on the neurokinin receptor revealed that an agonist peptide binds with biphasic... 

The mutual complementation of the different methods was examined in more detail for four selected molecules rofecoxib (COX-2), celecoxib (COX-2), indinavir (HIV protease), and lanepitant (neurokinin receptor). The results are shown in the form of Euler-Venn diagrams in Fig. 3.7. Apparently the methods complement each other. Each method was able to retrieve actives which were not found by the other methods. Interestingly, the performance of the different descriptors varied significantly within one class of ligands (compare, e.g., rofecoxib and celecoxib). 

Neurokinin receptor ligands - there are two types of NK receptors in the brain. NK2 agonists have been found to be anxiogenic while the antagonists are anxiolytic at least in animal studies. Some NK1 antagonists have also been shown to be anxiolytic in experimental studies. 

Walsh DA, Hu DE, Mapp PI, Polak JM, Blake DR, Fan TP. Innervation and neurokinin receptors during angiogenesis in the rat sponge granuloma. Histochem J 1996 28 759-769. 

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